Ataxia with isolated vitamin E deficiency: neurological phenotype, clinical follow-up and novel mutations in TTPA gene in Italian families

Neurol Sci. 2004 Jul;25(3):130-7. doi: 10.1007/s10072-004-0246-z.


Ataxia with vitamin E deficiency (AVED) is a rare autosomal recessive neurodegenerative disorder due to mutations in the alpha-tocopherol transfer protein (TTPA) gene on chromosome 8q13. AVED patients have progressive spinocerebellar symptoms and markedly reduced plasma levels of vitamin E. We studied neurological phenotype at diagnosis, and long-term effect of vitamin E supplementation in 16 patients from 12 Italian families. The most common mutations were the 744delA and 513insTT. Two novel TTPA mutations were identified: a severe truncating mutation (219insAT) in a homozygous patient, and a Gly246Arg missense mutation (G246R) in a compound heterozygous patient. The missense mutation was associated with a mild and slowly progressive form of the disease. Vitamin E supplementation therapy allowed a stabilization of the neurological conditions in most of the patients. However, development of spasticity and retinitis pigmentosa was noted in a few patients during therapy. Prompt genetic characterization of AVED patients may allow an effective early treatment and an adequate genetic counseling.

MeSH terms

  • Adolescent
  • Adult
  • Ataxia / diagnosis
  • Ataxia / genetics*
  • Ataxia / therapy
  • Carrier Proteins / genetics*
  • Female
  • Follow-Up Studies
  • Humans
  • Italy
  • Male
  • Middle Aged
  • Mutation*
  • Nervous System Diseases / diagnosis
  • Nervous System Diseases / genetics
  • Nervous System Diseases / therapy
  • Pedigree
  • Phenotype*
  • Vitamin E / therapeutic use
  • Vitamin E Deficiency / diagnosis
  • Vitamin E Deficiency / genetics*
  • Vitamin E Deficiency / therapy


  • Carrier Proteins
  • alpha-tocopherol transfer protein
  • Vitamin E